This invention relates to the treatment of cancer in animals, especially humans, using dendritic polymer conjugates.
The prospect of using dendritic polymers as carriers for drug delivery has been previously proposed on account of the unique structure and characteristics of these polymer molecules. More specifically, it has been proposed that the external surface functionality and interior morphological characteristics of dendritic polymer molecules appear to be very promising for developing new methods for controlling drug release and targeted drug delivery systems. However, relatively little work has been done in specific areas of drug delivery. In particular, the use of dendritic polymers as effective carriers for specific anti-tumor agents has not heretofore been demonstrated.
Certain platinum containing compounds, particularly carboplatin and cisplatin, have been used in the treatment of ovarian cancer, lung cancer, testicular cancer, breast cancer, stomach cancer and lymphoma. However, because of the non-specific toxicity and poor water solubility of these platinum containing compounds, the use of carboplatin and cisplatin has been relatively limited.
In order to overcome the non-specific toxicity and water solubility problems associated with cisplatin and carboplatin, it has been proposed to use linear polymers as carriers for these drugs. However, the use of linear polymers as carriers in drug delivery systems has several disadvantages. A major disadvantage with linear polymer drug carriers is that they are heterogenous, polydisperse compositions containing various different molecular weight polymer molecules. Because linear polymer compositions are not comprised of molecules having a precisely defined structure, it is more difficult to maintain uniform polymer properties, drug delivery properties, and therapeutic efficacy. As a result, it is relatively difficult to obtain FDA approval of the linear polymer-drug composites. Another disadvantage with the use of linear polymers as drug-carriers is that the location, and hence the availability, of the drug is difficult to control. In particular, the drug can become permanently bound within the polymer, making the drug unavailable for its intended therapeutic purpose. The tendency of the drug to become buried in the linear polymer leads to greater unpredictability on account of the non-uniform or heterogenous properties of the linear polymer molecules, and results in reduced drug efficiency because a significant proportion of the drug molecules are not effectively presented to the cell being treated.
Accordingly, it would be highly desirable to provide a precisely defined drug delivery system for platinum containing anti-tumor agents which exhibits high drug efficiency, high drug carrying capacity, good water solubility, good stability on storage, reduced toxicity, and improved anti-tumor activity in vivo.
This invention pertains to dendritic polymer conjugates which are useful drug delivery systems for carrying platinum containing anti-tumor agents to malignant tumors. The invention also pertains to methods of treating malignant tumors using the dendritic polymer conjugates, and to a method of preparing a dendritic polymer platinate useful for carrying platinum containing anti-tumor agents to malignant tumors.
The dendritic polymer platinates of this invention comprise a dendritic polymer conjugated to a platinum containing compound. The dendritic polymer platinates are prepared by obtaining a dendritic polymer having functional groups which are accessible to a platinum containing compound capable of interacting with the functional groups, contacting the dendritic polymer with the platinum containing compound, and reacting the dendritic polymer with the platinum containing compound. The dendritic polymer platinates are administered to an animal having a malignant tumor in an amount which is effective to inhibit growth of the malignant tumor, preferably intravenously, although other methods such as oral, parental, subcutaneous or topical administration are also envisioned.